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Evidence suggests obesity during pregnancy is associated with offspring attention-deficit hyperactivity disorder. However, studies have been limited to evaluating the association at a single age with inadequate data on important maternal lifestyle confounders and unmeasured familial confounding. The objective of this study was to examine the association between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 3, 5 and 8 years. Data came from the EDEN mother-child cohort. Maternal pre-pregnancy BMI status (kg/m 2 ) was calculated using pre-pregnancy weight and height (self-reported by mothers or measured by midwives). HIS were assessed by parental-report on the Strengths and Difficulties Questionnaire at 3, 5 and 8 years of age and used to derive developmental trajectories of HIS (n = 1428). Multivariate models were adjusted for confounders including socioeconomic status, maternal lifestyle behaviours (exercise, diet, smoking, alcohol), childcare and a stimulating home environment. Paternal BMI was used as a negative control. Compared to a normal pre-pregnancy BMI, pre-pregnancy maternal obesity was positively associated with increased odds of a high HIS trajectory between 3 and 8 years old in both unadjusted and adjusted logistic regression (adjusted odds ratio [aOR] 1.87 [95% CI 1.12, 3.12]). Pre-pregnancy overweight was not significantly associated after adjustment for confounders (aOR 1.32 [0.87, 2.01]). Maternal pre-pregnancy obesity, but not overweight, was associated with increased likelihood of a high HIS trajectory in children from 3 to 8 years old. This association persisted despite controlling for many important maternal lifestyle factors and paternal BMI. Further research is warranted to identify possible mediators involved., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and highly heritable neurodevelopmental disorder of major societal concern. Diagnosis can be challenging and there are large knowledge gaps regarding its etiology, though studies suggest an interplay of genetic and environmental factors involving epigenetic mechanisms. MicroRNAs (miRNAs) show promise as biomarkers of human pathology and novel therapies, and here we aimed to identify blood miRNAs associated with traits of ADHD as possible biomarker candidates and further explore their biological relevance., Methods: Our study population consisted of 1126 children (aged 5-12 years, 46% female) from the Human Early Life Exposome study, a study spanning six ongoing population-based European birth cohorts. Expression profiles of miRNAs in whole blood samples were quantified by microarray and tested for association with ADHD-related measures of behavior and neuropsychological functions from questionnaires (Conner's Rating Scale and Child Behavior Checklist) and computer-based tests (the N-back task and Attention Network Test)., Results: We identified 29 miRNAs significantly associated (false discovery rate < .05) with the Conner's questionnaire-rated trait hyperactivity, 15 of which have been linked to ADHD in previous studies. Investigation into their biological relevance revealed involvement in several pathways related to neurodevelopment and function, as well as being linked with other neurodevelopmental or psychiatric disorders known to overlap with ADHD both in symptomology, genetic risk, and co-occurrence, such as autism spectrum disorder or schizophrenia. An additional three miRNAs were significantly associated with Conner's-rated inattention. No associations were found with questionnaire-rated total ADHD index or with computer-based tests., Conclusions: The large overlap of our hyperactivity-associated miRNAs with previous studies on ADHD is intriguing and warrant further investigation. Though this study should be considered explorative and preliminary, these findings contribute towards identifying a set of miRNAs for use as blood-based biomarkers to aid in earlier and easier ADHD diagnosis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Perinatal maternal depression and anxiety are associated with adverse maternal outcomes, and nutrition may play an important role in their emergence. Previous research shows that certain micro and macronutrients found in different dietary patterns may associate with perinatal mood disorders. This study aims to explore relationships between nutrition during pregnancy and perinatal maternal depression and anxiety symptoms using network analyses., Methods: Using data from the French EDEN mother-child cohort, the sample consisted of 1438 women with available mental health outcomes (CES-D, STAI and EPDS) and nutritional markers collected from food frequency questionnaires. Four networks were constructed to explore the relationships between prenatal nutrient status, dietary patterns, and perinatal mental health, while accounting for important confounders., Results: The Healthy dietary pattern was associated with the presence of vital micronutrients, while the Western dietary pattern was consistently associated with poorer intake of specific micronutrients and contained an excess of certain macronutrients. Western dietary pattern and symptoms of postnatal depression were connected by a positive edge in both the macronutrient and micronutrient networks. Lower education levels were associated with higher Western dietary pattern scores, from which a positive edge linked to postnatal depression symptoms in both models., Conclusions: A Western dietary pattern was associated with increased symptoms of postnatal depression in our adjusted network models; The Healthy dietary pattern was associated with essential micronutrients but not with symptoms of depression or anxiety. Perinatal mental health might be impacted by specific dietary patterns in the context of psychosocial and physical stress associated with pregnancy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The placenta is a key organ for fetal and brain development. Its epigenome can be regarded as a biochemical record of the prenatal environment and a potential mechanism of its association with the future health of the fetus. We investigated associations between placental DNA methylation levels and child behavioral and emotional difficulties, assessed at 3 years of age using the Strengths and Difficulties Questionnaire (SDQ) in 441 mother-child dyads from the EDEN cohort. Hypothesis-driven and exploratory analyses (on differentially methylated probes (EWAS) and regions (DMR)) were adjusted for confounders, technical factors, and cell composition estimates, corrected for multiple comparisons, and stratified by child sex. Hypothesis-driven analyses showed an association of cg26703534 ( AHRR ) with emotional symptoms, and exploratory analyses identified two probes, cg09126090 (intergenic region) and cg10305789 ( PPP1R16B ), as negatively associated with peer relationship problems, as well as 33 DMRs, mostly positively associated with at least one of the SDQ subscales. Among girls, most associations were seen with emotional difficulties, whereas in boys, DMRs were as much associated with emotional than behavioral difficulties. This study provides the first evidence of associations between placental DNA methylation and child behavioral and emotional difficulties. Our results suggest sex-specific associations and might provide new insights into the mechanisms of neurodevelopment.

Background: Early-life environmental exposures are suspected to be involved in the development of chronic diseases later in life. Most studies conducted so far considered single or few exposures and single-health parameter. Our study aimed to identify a childhood general health score and assess its association with a wide range of pre- and post-natal environmental exposures., Methods: The analysis is based on 870 children (6-12 years) from six European birth cohorts participating in the Human Early-Life Exposome project. A total of 53 prenatal and 105 childhood environmental factors were considered, including lifestyle, social, urban and chemical exposures. We built a general health score by averaging three sub-scores (cardiometabolic, respiratory/allergy and mental) built from 15 health parameters. By construct, a child with a low score has a low general health status. Penalized multivariable regression through Least Absolute Shrinkage and Selection Operator (LASSO) was fitted in order to identify exposures associated with the general health score., Findings: The results of LASSO show that a lower general health score was associated with maternal passive and active smoking during pregnancy and postnatal exposure to methylparaben, copper, indoor air pollutants, high intake of caffeinated drinks and few contacts with friends and family. Higher child's general health score was associated with prenatal exposure to a bluespace near residency and postnatal exposures to pets, cobalt, high intakes of vegetables and more physical activity. Against our hypotheses, postnatal exposure to organochlorine compounds and perfluorooctanoate were associated with a higher child's general health score., Conclusion: By using a general health score summarizing the child cardiometabolic, respiratory/allergy and mental health, this study reinforced previously suspected environmental factors associated with various child health parameters (e.g. tobacco, air pollutants) and identified new factors (e.g. pets, bluespace) warranting further investigations., (© 2023. The Author(s).)

Childhood internalizing disorders refer to inwardly focused negative behaviours such as anxiety, depression, and somatic complains. Interactions between psychosocial, genetic, and environmental risk factors adversely impact neurodevelopment and can contribute to internalizing disorders. While prenatal exposure to single endocrine disruptors (EDs) is associated with internalizing behaviours in infants, the associations with prenatal exposure to EDs in mixture remain poorly addressed. In addition, the biological mediators of EDs in mixture effects on internalizing behaviours remain unexplored. EDs do not only interfere with endocrine function, but also with immune function and inflammatory processes. Based on this body of evidence, we hypothetised that inflammation at birth is a plausible biological pathway through which prenatal exposure to EDs in mixture could operate to influence offspring internalizing behaviours. Based on the EDEN birth cohort, we investigated whether exposure to a mixture of EDs increased the odds of internalizing disorders in 459 boy infants at age 3, and whether the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α measured at birth were mediators of this effect. To determine both the joint and individual associations of prenatal exposure to EDs with infant internalizing behaviours and the possible mediating role of cytokines, we used the counterfactual hierarchical Bayesian Kernel Machine Regression (BKMR) regression-causal mediation analysis. We show that prenatal exposure to a complex mixture of EDs has limited effects on internalizing behaviours in boys at age 3. We also show that IL-1β, IL-6, and TNF-α are unlikely mediators or suppressors of ED mixture effects on internalizing behaviours in boys at age 3. Further studies on larger cohorts are warranted to refine the deleterious effects of EDs in mixtures on internalizing behaviours and identify possible mediating pathways., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Glaichenhaus reports financial support was provided by Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail and Université Côte d'Azur. Davidovic reports financial support was provided by Fondation de France., (Copyright © 2023. Published by Elsevier Inc.)

Background: Ambient temperature, particularly heat, is increasingly acknowledged as a trigger for preterm delivery but study designs have been limited and results mixed. We aimed to comprehensively evaluate the association between ambient temperature throughout pregnancy and preterm delivery., Methods: We estimated daily temperature throughout pregnancy using a cutting-edge spatiotemporal model for 5347 live singleton births from three prospective cohorts in France, 2002-2018. We performed Cox regression (survival analysis) with distributed lags to evaluate time-varying associations with preterm birth simultaneously controlling for exposure during the first 26 weeks and last 30 days of pregnancy. We examined weekly mean, daytime, night-time and variability of temperature, and heatwaves accounting for adaptation to location and season., Results: Preterm birth risk was higher following cold (5th vs 50th percentile of mean temperature) 7-9 weeks after conception [relative risk (RR): 1.3, 95% CI: 1.0-1.6 for 2°C vs 11.6°C] and 10-4 days before delivery (RR: 1.6, 95% CI: 1.1-2.1 for 1.2°C vs 12.1°C). Night-time heat (95th vs 50th percentile of minimum temperature; 15.7°C vs 7.4°C) increased risk when exposure occurred within 5 weeks of conception (RR: 2.0, 95% CI: 1.05-3.8) or 20-26 weeks after conception (RR: 2.9, 95% CI: 1.2-6.8). Overall and daytime heat (high mean and maximum temperature) showed consistent effects. We found no clear associations with temperature variability or heatwave indicators, suggesting they may be less relevant for preterm birth., Conclusions: In a temperate climate, night-time heat and chronic and acute cold exposures were associated with increased risk of preterm birth. These results suggest night-time heat as a relevant indicator. In the context of rising temperatures and more frequent weather hazards, these results should inform public health policies to reduce the growing burden of preterm births., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project., Methods: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures., Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts., Conclusion: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Objective: Although preterm-born and low-birth-weight individuals have an increased risk of cardiovascular diseases in adulthood, little is known regarding early cardiovascular and renal damage (CVRD) or hypertension in adulthood. Our study investigated the association of birth weight with early CVRD markers as well as the heritability of birth weight in an initially healthy family-based cohort., Methods: This study was based on 1028 individuals from the familial longitudinal STANISLAS cohort (399 parents/629 children) initiated in 1993-1995, with a fourth examination conducted in 2011-2016. Analyses performed at the fourth visit included pulse-wave velocity, central pressure, ambulatory blood pressure, hypertension status, diastolic dysfunction/distensibility, left ventricular mass indexed (LVMI), carotid intima-media thickness and kidney damage. The family structure of the cohort allowed birth weight heritability estimation., Results: Mean (±SD) birth weight was 3.3 ± 0.6 kg. Heritability was moderate (42-44%). At the fourth visit, individuals were 37 years old (32.0-57.0), 56% were women and 13% had antihypertensive treatment. Birth weight was strongly and negatively associated with hypertension [odds ratio (OR) 95% confidence interval (CI) 0.61 (0.45-0.84)]. A nonlinear association was found with LVMI, participants with a birth weight greater than 3 kg having a higher LVMI. A positive association ( β 95% CI 5.09 (1.8-8.38)] was also observed between birth weight and distensibility for adults with normal BMI. No associations were found with other CVRD., Conclusion: In this middle-aged population, birth weight was strongly and negatively associated with hypertension, and positively associated with distensibility in adults with normal BMI and with LVMI for higher birth weights. No associations were found with other CVRD markers., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although the deleterious effect of micronutrient deficiency at sensitive periods on neurodevelopment is well established, the potential influence of macronutrient intake on early life neurodevelopment of healthy term infants has been seldomly studied. We aimed to explore whether macronutrient intake at 12 months was related to neurodevelopmental scores in preschool children., Methods: Analyses were based on data from the EDEN mother-child cohort. Macronutrient intake was assessed by 3-day food records at 12 months of age. Neurodevelopment was assessed at 3 years using the French version of the Ages and Stages Questionnaire (ASQ) (n = 914), and at 5-6 years, using the French version of the Wechsler Preschool and Primary Scale of Intelligence-Third Edition (n = 785). An association between macronutrient intake and neurodevelopmental scores were analysed by multivariable linear regression for 3-year Full Score ASQ or 5-6-year intelligence quotient scores and multivariable logistic regression for 3-year ASQ subdomains., Results: Macronutrient intake in infancy was not associated with neurodevelopmental scores in preschool children. No association was found between PUFA intake and overall neurodevelopmental scores, after accounting for multiple testing., Conclusion: In the present study, macronutrient intake at one year did not appear to influence the child's cognitive ability at 3 and 5-6 years. Further studies are needed to clarify the relationship between early fatty acid intake and neurodevelopment., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: High prevalence of overweight and obesity already observed in preschool children suggests the involvement of early-life risk factors. Preconception period and pregnancy are crucial windows for the implementation of child obesity prevention interventions with parental lifestyle factors as relevant targets. So far, most studies have evaluated their role separately, with only a few having investigated their potential synergistic effect on childhood obesity. Our objective was to investigate parental lifestyle patterns in the preconception and pregnancy periods and their association with the risk of child overweight after 5 years., Materials and Methods: We harmonized and interpreted results from four European mother-offspring cohorts participating in the EndObesity Consortium [EDEN, France; Elfe, France; Lifeways, Ireland; and Generation R, Netherlands] with data available for 1,900, 18,000, 1,100, and 9,500 families, respectively. Lifestyle factors were collected using questionnaires and included parental smoking, body mass index (BMI), gestational weight gain, diet, physical activity, and sedentary behavior. We applied principal component analyses to identify parental lifestyle patterns in preconception and pregnancy. Their association with risk of overweight (including obesity; OW-OB) and BMI z -scores between 5 and 12 years were assessed using cohort-specific multivariable logistic and linear and regression models (adjusted for potential confounders including parental age, education level, employment status, geographic origin, parity, and household income)., Results: Among the various lifestyle patterns derived in all cohorts, the two explaining the most variance were characterized by (1) "high parental smoking, low maternal diet quality (and high maternal sedentary behavior in some cohorts)" and, (2) "high parental BMI and low gestational weight gain." Patterns characterized by high parental BMI, smoking, low diet quality or high sedentary lifestyle before or during pregnancy were associated with higher risk of OW-OB in children, and BMI z -score at any age, with consistent strengths of associations in the main cohorts, except for lifeways., Conclusion: This project provides insight into how combined parental lifestyle factors in the preconception and pregnancy periods are associated with the future risk of child obesity. These findings are valuable to inform family-based and multi-behavioural child obesity prevention strategies in early life., Competing Interests: JH owns controlling interest in Connecting Health Innovations, a company that has licensed the right to his invention of the dietary inflammatory index from the University of South Carolina to develop computer and smart phone applications for patient counselling and dietary intervention in clinical settings. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lecorguillé, Schipper, O’Donnell, Aubert, Tafflet, Gassama, Douglass, Hébert, de Lauzon-Guillain, Kelleher, Charles, Phillips, Gaillard, Lioret and Heude.)

A converging body of evidence from neuroimaging, behavioral, and neuropsychology studies suggests that different arithmetic operations rely on distinct neuro-cognitive processes: while addition and subtraction may rely more on visuospatial reasoning, multiplication would depend more on verbal abilities. In this paper, we tested this hypothesis in a longitudinal study measuring language and visuospatial skills in 358 preschoolers, and testing their mental calculation skills at the beginning of middle school. Language skills at 5.5 years significantly predicted multiplication, but not addition nor subtraction scores at 11.5 years. Conversely, early visuospatial skills predicted addition and subtraction, but not multiplication scores. These results provide strong support for the existence of a double dissociation in mental arithmetic operations, and demonstrate the existence of long-lasting links between language/visuospatial skills and specific calculation abilities., (© 2022 John Wiley & Sons Ltd.)

Aims: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age., Methods and Results: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant., Conclusion: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease., Competing Interests: Conflict of interest: D.A.L. reported grants from national and international government and charity funders, Roche Diagnostics, and Medtronic Ltd for work unrelated to this publication. S.M.N. reported grants from Roche Diagnostics, Access Fertility, Modern Fertility, Ferring Pharmaceuticals, TFP, and Merck for work unrelated to this publication. The other authors report no conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: High-dimensional mediation analysis is an extension of unidimensional mediation analysis that includes multiple mediators, and increasingly it is being used to evaluate the indirect omics-layer effects of environmental exposures on health outcomes. Analyses involving high-dimensional mediators raise several statistical issues. Although many methods have recently been developed, no consensus has been reached about the optimal combination of approaches to high-dimensional mediation analyses., Objectives: We developed and validated a method for high-dimensional mediation analysis (HDMAX2) and applied it to evaluate the causal role of placental DNA methylation in the pathway between exposure to maternal smoking (MS) during pregnancy and gestational age (GA) and birth weight of the baby at birth., Methods: HDMAX2 combines latent factor regression models for epigenome-wide association studies with max 2 tests for mediation and considers CpGs and aggregated mediator regions (AMRs). HDMAX2 was carefully evaluated using simulated data and compared to state-of-the-art multidimensional epigenetic mediation methods. Then, HDMAX2 was applied to data from 470 women of the Etude des Déterminants pré et postnatals du développement de la santé de l'Enfant (EDEN) cohort., Results: HDMAX2 demonstrated increased power in comparison with state-of-the-art multidimensional mediation methods and identified several AMRs not identified in previous mediation analyses of exposure to MS on birth weight and GA. The results provided evidence for a polygenic architecture of the mediation pathway with a posterior estimate of the overall indirect effect of CpGs and AMRs equal to 44.5 g lower birth weight representing 32.1% of the total effect [standard deviation ( SD ) = 60.7 g ]. HDMAX2 also identified AMRs having simultaneous effects both on GA and on birth weight. Among the top hits of both GA and birth weight analyses, regions located in COASY , BLCAP , and ESRP2 also mediated the relationship between GA and birth weight, suggesting reverse causality in the relationship between GA and the methylome., Discussion: HDMAX2 outperformed existing approaches and revealed an unsuspected complexity of the potential causal relationships between exposure to MS and birth weight at the epigenome-wide level. HDMAX2 is applicable to a wide range of tissues and omic layers. https://doi.org/10.1289/EHP11559.

Background: Given inconsistent results in the literature, our objective was to examine the role of early parental feeding practices in children's growth., Methods: Analyses were based on 1245 children from the EDEN mother-child cohort. Parental feeding practices were assessed at the 2-year follow-up by using the Comprehensive Feeding Practices Questionnaire. International Obesity Task Force BMI z-scores were derived from weight and height assessed at 2, 4, 6, and 8 years. Associations between parental feeding practices and child BMI z-scores at 4, 6 and 8 years were assessed by multivariable linear regressions, notably adjusted for 2-year BMI z-score. Analyses were stratified by child sex when relevant. Moreover, interaction and mediation analyses were respectively performed to assess whether parental feeding practices could moderate or mediate the associations between early and later growth., Results: For a given BMI z-score at 2 years, parental restriction for weight at 2 years was positively associated with child BMI z-scores from 4 to 8 years (at 8 years: β [95% CI] = 0.09 [0.01; 0.16]). Among boys only, high use of food as a reward was positively associated with later BMI z-scores (at 8 years: β [95% CI] = 0.15 [0.03; 0.27]). Parental feeding practices were not moderating factors in the associations between early and later growth. Parental restriction for weight was a mediating factor in the associations between 2-year BMI z-score and BMI z-scores up to 8 years (mediation: 2.69% [0.27%; 5.11%] of the total effect at 8 years)., Conclusions: Restriction for weight reasons, often used by parents in response to the child's high appetite in infancy, appears to lie on the pathway between early and later BMI, but not restriction for health, suggesting that parental way of restricting the child's food intake matters., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking., Methods: The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years [ N  = 519, mean (SD) age, 13.0 (2.9) years; 46.4% male], and who were measured with cIMT, vascular-related and metabolic-related proteins at a median follow-up of 19 ± 2 years. BMI, waist-to-height ratio and waist circumference were converted to age-specific and sex-specific z -scores., Results: A minority of children were overweight/obese (16.2% overweight-BMI z -score >1; 1.3% obesity- z -score >2). Higher BMI, waist-height ratio and waist circumference in children were significantly associated with greater adult cIMT in univariable analysis, although not after adjusting for C-reactive protein. These associations were more pronounced in those with consistently high adiposity status from childhood to middle adulthood. Participants with higher adiposity during childhood (BMI or waist-height ratio) had higher levels of insulin-like growth factor-binding protein-1, protein-2, matrix metalloproteinase-3, osteopontin, hemoglobin and C-reactive protein in adulthood. Network analysis showed that IL-6, insulin-like growth factor-1 and fibronectin were the key proteins associated with childhood adiposity., Conclusion: In a population-based cohort followed for 20 years, higher BMI or waist-to-height ratio in childhood was significantly associated with greater cIMT and enhanced levels of proteins reflective of inflammation, supporting the importance of inflammation as progressive atherosclerosis in childhood adiposity., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A high prevalence of excess weight in children younger than 5 years suggests the involvement of early-life risk factors. The preconception and pregnancy periods are crucial stages for the implementation of interventions to prevent childhood obesity. Most studies so far have evaluated the effects of early-life factors separately, with only a few investigating the combined effect of parental lifestyle factors. Our objective was to fill the literature gap regarding parental lifestyle factors in the preconception and pregnancy periods and to study their association with the risk of overweight in children after the age of 5 years., Methods: We harmonised and interpreted data from four European mother-offspring cohorts (EDEN [comprising 1900 families], Elfe [comprising 18 000 families], Lifeways [comprising 1100 families], and Generation R [comprising 9500 families]). Written informed consent was obtained from parents of all involved children. Lifestyle factor data collected through questionnaires comprised parental smoking, BMI, gestational weight gain, diet, physical activity, and sedentary behaviour. We applied principal component analyses to identify multiple lifestyle patterns in preconception and pregnancy. Their association with child BMI z-score and risk of overweight (including obesity, overweight and obesity, as defined by the International Task Force reference) between the ages of 5 and 12 years were assessed using cohort-specific multivariable linear and logistic regression models (adjusted for confounders including parental age, education level, employment status, geographic origin, parity, and household income)., Findings: Among the various lifestyle patterns identified in all cohorts, the two that better explained variance were high parental smoking plus low maternal diet quality or high maternal sedentary behaviour, and high parental BMI plus low gestational weight gain. Overall, we observed that patterns characterised by high parental BMI, smoking, low-quality diet, or sedentary lifestyle before or during pregnancy were associated with higher BMI z-scores and risk of overweight and obesity in children aged 5-12 years., Interpretation: Our data contribute to a better understanding of how parental lifestyle factors might be associated with the risk of childhood obesity. These findings are valuable to inform future family-based and multi-behavioural child obesity prevention strategies in early life., Funding: European Union's Horizon 2020 under the ERA-NET Cofund action (reference 727565) and European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL, EndObesity)., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Long-term consequences of impaired fetal growth are well documented for cardiometabolic outcomes. We propose an outcome-wide analysis of the association between birth weight (BW) and long-term health in a large contemporary adult cohort., Methods: The study included 73,315 participants under 60 years with a reliable BW from the French nationwide Constances cohort. Low and high BW (LBW/HBW) were defined as BW<10th and >90th of sex-specific percentiles. Associations between BW and outcomes were analyzed with a sex-stratified modified Poisson regression adjusted for the participant's age, maternal health history, geographical origins, and parents' occupation., Results: Mean BW (10 th -90 th percentile) was 3390 g (2800-4000) for men and 3247g (2680-3820) for women. In men, LBW was associated with (RR [CI95]): fasting glucose impairment (1.33 [1.16;1.52]); hypertriglyceridemia (1.27 [1.17;1.37]); high blood pressure (HBP) (1.15 [1.07;1.24]); non-alcoholic fatty liver disease NAFLD (1.13 [1.02;1.24]); high LDL-cholesterol (1.12 [1.05;1.21]); anxiety (1.12 [1.01;1.24]) and depression (1.09 [1.00;1.18]). HBW was associated with obesity (1.21 [1.08;1.35]). In women, LBW was associated with fasting glucose impairment (1.31 [1.12;1.54]); HBP (1.27 [1.16;1.4]); hypertriglyceridemia (1.20 [1.05;1.36]); anxiety (1.10 [1.03;1.17]); and asthma (1.09 [1;1.19}). HBW was associated with obesity (1.24 [1.13;1.36]) and NAFLD (1.20 [1.06;1.37). LBW and HBW were associated with a lesser likelihood of tertiary education attainment in both sexes. Participants' education level was a significant partial mediator of the association between LBW and outcomes., Conclusion: Extreme BW is associated with long-term health. It should be considered in the personalized prevention of cardiometabolic, respiratory, and mental health conditions in adulthood, especially in socio-economically disadvantaged populations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Few studies have investigated longitudinal trajectories of child socioemotional and behavioural development in relation to maternal prenatal mental health exposure or taken into consideration of the potential buffering effects of psychological intervention during pregnancy. Using data from 1135 mother-child dyads from the EDEN cohort from the general French population, Group-based trajectory modelling was used to model trajectories of behavioural and emotional characteristics measured at four timepoints via a parent-administered Strengths and Difficulties Questionnaire. Using propensity scores and inverse probability weighting to account for confounding factors, multinomial logistic regressions were used to quantify the associations with maternal symptoms of prenatal depression and anxiety. Stratified analyses were conducted by reporting psychologist and psychiatrist consultations during pregnancy. Compared to those without psychological problems, children of mothers with comorbid anxiety and depression retained a higher probability of following high and intermediate trajectories of emotional problems and a high trajectory of conduct problems throughout childhood. This increased risk was not present in the children of mothers who sought support through a prenatal psychologist or psychiatrist consultation. This article adds to a body of evidence underlining the importance of mental health care for expecting mothers.

Background: Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence., Methods and Findings: We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries., Conclusions: This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DAL has received support from Roche Diagnostics and Medtronic in relation to biomarker research that is not related to the research presented in this paper. The other authors have declared that no competing interests exist., (Copyright: © 2023 Vinther et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that results from a complex interaction between genes and environment. Breastfeeding (BF) is thought to promote healthy cognitive development, and a body of research has suggested that it may also protect against ASD. Our objectives were to identify the relationship between the initiation and duration of BF and the severity of clinical presentation in ASD. Data were collected from 243 children with a confirmed diagnosis of ASD followed in the ELENA cohort. Clinical severity was measured according to multiple dimensions using standardised tools. The frequency of the initiation of BF was comparable to that of the general population and the rate of children still being breastfed at six months of age was higher. Our results did not indicate a contribution of initiation or duration of BF to the prevention of clinical severity of ASD. We discuss our results in the light of possible methodological limitations of previous reports of an association between BF and ASD.Clinical Trial Registration: NCT02625116., (© 2023. The Author(s).)

Background: Children's energy balance-related behaviours (EBRB), comprising diet, screen time, physical activity, and sleep, combine into "lifestyle patterns", which may exert a synergistic effect on health. To date, studies investigating this synergy have primarily focused on obesity risk, without addressing other facets of health., Objectives: To examine the prospective associations of preschoolers' lifestyle patterns with socio-emotional, behavioural, and body mass index (BMI) outcomes at 8 years., Methods: Participants were 876 children from the EDEN mother-child cohort. Three lifestyle patterns (unhealthy, healthy, and mixed) were previously identified at age 5, separately in boys and girls. At age 8, height and weight measures generated BMI z-scores while social-emotional and behavioural development was assessed by parents using the Strengths and Difficulties Questionnaire (SDQ). Drawing from the outcome-wide approach, sex- and outcome-specific adjusted linear regressions were fitted., Results: Boys' adherence to a healthy lifestyle pattern (combining a nutrient-dense diet and limited screen time) at 5 years was positively associated with prosocial behaviours (β = 0.14; 95% confidence interval [CI] 0.01, 0.26) and inversely related to hyperactivity-inattention symptoms (β = -0.12; 95% CI -0.23, -0.01) at 8 years. Girls' mixed lifestyle pattern (sugar or artificially sweetened beverages, high screen, physical activity and low sleep times) was associated with prosocial behaviours (β = 0.12; 95% CI 0.01, 0.23). There was no evidence of associations between lifestyle patterns and BMI z-scores., Conclusions: Findings suggest synergistic benefits of engaging in a combination of optimal EBRBs, especially in boys, and support intervention efforts at preschool age to enhance some dimensions of their later socio-emotional and behavioural development., (© 2022 John Wiley & Sons Ltd.)

This narrative systematic review examined effectiveness of interventions during pregnancy and up to 2 years of age in improving energy balance-related behaviors or prevent overweight/obesity in children from families experiencing socio-economic disadvantage. We identified 24 interventions, from 33 articles, since 1990. Overall, despite their heterogeneity and variability in internal and external validity, there was some evidence of beneficial impact of interventions on obesity risk (4/15), and associated behaviors, e.g.: breastfeeding (9/18), responsive feeding (11/16), diet (7/8), sedentary (1/3) and movement (4/7) behaviors, and sleep (1/2). The most effective interventions aimed at promoting breastfeeding commenced antenatally; this was similar for the prevention of obesity, provided the intervention continued for at least 2 years postnatally and was multi-behavioral. Effective interventions were more likely to target first-time mothers and involve professional delivery agents, multidisciplinary teams and peer groups. Among ethnic/racial minorities, interventions delivered by lay agents had some impact on dietary behavior but not weight outcomes. Co-creation with stakeholders, including parents, and adherence to theoretical frameworks were additional ingredients for more pragmatic, inclusive, non-judgmental, and effective programs. The growing body of evidence on obesity prevention interventions targeting families experiencing socio-economic disadvantage is promising for reducing early inequalities in obesity risk., (© 2022 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

We investigated the associations between maternal diet quality and allergic and respiratory diseases in children. Analyses were based on 1316 mother-child pairs from the EDEN mother-child cohort. Maternal diet quality during pregnancy was assessed through a food-based score (the Diet Quality), a nutrient-based score (the PANDiet), and the adherence to guidelines for main food groups. Clusters of allergic and respiratory multimorbidity clusters up to 8 years were identified using Latent Class Analysis. Associations were assessed by adjusted multinomial logistic regressions. Four clusters were identified for children: "asymptomatic" (67%, reference group), "asthma only" (14%), "allergies without asthma" (12%), "multi-allergic" (7%). These clusters were not associated with mother diet quality assessed by both scores. Children from mothers consuming legumes once a month or less were at higher risk of belonging to the "multi-allergic" cluster (odds ratio (OR) (95% confidence interval (95%CI)) = 1.60 (1.01;2.54)). No association was found with other food groups or other clusters. In our study, allergic and respiratory multimorbidity in children was described with four distinct clusters. Our results suggest an interest in legumes consumption in the prevention of allergic diseases but need to be confirmed in larger cohorts and randomized control trials.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings., (© 2022. The Author(s).)

Background: Mediation analysis aims at estimating to what extent the effect of an exposure on an outcome is explained by a set of mediators on the causal pathway between the exposure and the outcome. The total effect of the exposure on the outcome can be decomposed into an indirect effect, i.e. the effect explained by the mediators jointly, and a direct effect, i.e. the effect unexplained by the mediators. However finer decompositions are possible in presence of independent or sequential mediators., Methods: We review four statistical methods to analyse multiple sequential mediators, the inverse odds ratio weighting approach, the inverse probability weighting approach, the imputation approach and the extended imputation approach. These approaches are compared and implemented using a case-study with the aim to investigate the mediating role of adverse reproductive outcomes and infant respiratory infections in the effect of maternal pregnancy mental health on infant wheezing in the Ninfea birth cohort., Results: Using the inverse odds ratio weighting approach, the direct effect of maternal depression or anxiety in pregnancy is equal to a 59% (95% CI: 27%,94%) increased prevalence of infant wheezing and the mediated effect through adverse reproductive outcomes is equal to a 3% (95% CI: -6%,12%) increased prevalence of infant wheezing. When including infant lower respiratory infections in the mediation pathway, the direct effect decreases to 57% (95% CI: 25%,92%) and the indirect effect increases to 5% (95% CI: -5%,15%). The estimates of the effects obtained using the weighting and the imputation approaches are similar. The extended imputation approach suggests that the small joint indirect effect through adverse reproductive outcomes and lower respiratory infections is due entirely to the contribution of infant lower respiratory infections, and not to an increased prevalence of adverse reproductive outcomes., Conclusions: The four methods revealed similar results of small mediating role of adverse reproductive outcomes and early respiratory tract infections in the effect of maternal pregnancy mental health on infant wheezing. The choice of the method depends on what is the effect of main interest, the type of the variables involved in the analysis (binary, categorical, count or continuous) and the confidence in specifying the models for the exposure, the mediators and the outcome., (© 2022. The Author(s).)

Environmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1301 mother-child pairs, we associate individual exposomes consisting of >100 chemical, outdoor, social and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, proteins and metabolites) in childhood. We identify 1170 associations, 249 in pregnancy and 921 in childhood, which reveal potential biological responses and sources of exposure. Pregnancy exposures, including maternal smoking, cadmium and molybdenum, are predominantly associated with child DNA methylation changes. In contrast, childhood exposures are associated with features across all omics layers, most frequently the serum metabolome, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions, among others. Our comprehensive and unique resource of all associations ( https://helixomics.isglobal.org/ ) will serve to guide future investigation into the biological imprints of the early life exposome., (© 2022. The Author(s).)

Background: Cord blood leptin is an indicator of neonatal fat mass and could shape postnatal adiposity trajectories. Investigating genetic polymorphisms of the leptin receptor gene (LEPR) could help understand the mechanisms involved., Objectives: We aimed to investigate the association of cord blood leptin level and the LEPR rs9436303 polymorphism, with body mass index (BMI) at adiposity peak (AP) and age at adiposity rebound (AR)., Methods: In the EDEN cohort, BMI at AP and age at AR were estimated with polynomial mixed models, for 1713 and 1415 children, respectively. Multivariable linear regression models allowed for examining the associations of cord blood leptin level and LEPR rs9436303 genotype with BMI at AP and age at AR adjusted for potential confounders including birth size groups. We also tested interactions between cord blood leptin level and rs9436303 genotype., Results: Increased leptin level was associated with reduced BMI at AP and early age at AR (comparing the highest quintile of leptin level to the others). Rs9436303 G-allele carriage was associated with increased BMI at AP and later age at AR but did not modulate the association with leptin level., Conclusion: These results illustrate the role of early life body composition and the intrauterine environment in the programming of adiposity in childhood., (© 2022 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

The objective of this study was to determine the relationship between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 5 years, including preterm and term-born children, and to determine whether this association varied with gestational age. Maternal pre-pregnancy BMI and offspring HIS were assessed in 10,898 participants born ≥ 33 weeks of gestation from the ELFE cohort and 2646 children born between 23 and 34 weeks from the EPIPAGE 2 cohort. Reported pre-pregnancy weight (kg) and measured height (m) were collected from mothers at inclusion and used to classify BMI (kg/m 2 ). Child HIS were evaluated using the Strengths and Difficulties Questionnaire around 5 years of age. Logistic regression estimated odds ratios (OR) of a high HIS score (≥ 90th percentile) in the ELFE cohort and generalized estimated equations were used in EPIPAGE 2 to account for non-independence of multiple births. As a negative control, paternal BMI was also considered as an exposure of interest in sensitivity analyses. Maternal pre-pregnancy obesity and overweight were associated with child HIS at 5 years in ELFE (adjusted OR [aOR] for obesity 1.27 [1.06, 1.53]; overweight aOR 1.16 [1.00, 1.36]) and pre-pregnancy obesity was associated with high HIS scores in preterm infants of EPIPAGE 2 (aOR 1.48 [1.06, 2.08]). In ELFE, the magnitude of the association increased with decreasing gestational age (interaction p = 0.02). High maternal pre-pregnancy BMI is associated with greater likelihood of high HIS scores in both at-term and preterm children at 5 years of age., (© 2022. The Author(s).)

Background: Maternal blood pressure levels reflect cardiovascular adaptation to pregnancy and proper maternal-fetal exchanges through the placenta and are very sensitive to numerous environmental stressors. Maternal hypertension during pregnancy has been associated with impaired placental functions and with an increased risk for children to suffer from cardiovascular and respiratory diseases later on. Investigating changes in placental DNA methylation levels and cell-type composition in association with maternal blood pressure could help elucidate its relationships with placental and fetal development., Methods: Taking advantage of a large cohort of 666 participants, we investigated the association between epigenome-wide DNA methylation patterns in the placenta, measured using the Infinium HumanMethylation450 BeadChip, placental cell-type composition, estimated in silico, and repeated measurements of maternal steady and pulsatile blood pressure indicators during pregnancy., Results: At the site-specific level, no significant association was found between maternal blood pressure and DNA methylation levels after correction for multiple testing (false discovery rate < 0.05), but 5 out of 24 previously found CpG associations were replicated (p-value < 0.05). At the regional level, our analyses highlighted 64 differentially methylated regions significantly associated with at least one blood pressure component, including 35 regions associated with mean arterial pressure levels during late pregnancy. These regions were found enriched for genes implicated in lung development and diseases. Further mediation analyses show that a significant part of the association between steady blood pressure-but not pulsatile pressure-and placental methylation can be explained by alterations in placental cell-type composition. In particular, elevated blood pressure levels are associated with a decrease in the ratio between mesenchymal stromal cells and syncytiotrophoblasts, even in the absence of preeclampsia., Conclusions: This study provides the first evidence that the association between maternal steady blood pressure during pregnancy and placental DNA methylation is both direct and partly explained by changes in cell-type composition. These results could hint at molecular mechanisms linking maternal hypertension to lung development and early origins of childhood respiratory problems and at the importance of controlling maternal blood pressure during pregnancy., (© 2022. The Author(s).)

Background & Aims: Maternal diet during pregnancy is a modifiable behaviour which plays an important role in maternal, neonatal and child health outcomes. Thus, knowledge of predictors of dietary quality and dietary inflammatory potential in European countries may contribute to developing maternal diet-related public health policies that target specific at-risk populations in Europe., Methods: We used harmonised data from >26,000 pregnant women enrolled in the ALSPAC, EDEN, Generation R, Lifeways, REPRO&#95;PL, ROLO and SWS cohorts, as part of the ALPHABET consortium. Maternal dietary quality and inflammatory potential were assessed using the Dietary Approaches to Stop Hypertension (DASH) and the energy-adjusted Dietary Inflammatory Index (E-DII). We conducted an individual participant data meta-analysis to investigate the maternal sociodemographic, health and behavioural predictors of maternal diet before and during pregnancy., Results: DASH and E-DII scores were moderately correlated: from -0.63 (95% CI: -0.66, -0.59) to -0.48 (95% CI: -0.49, -0.47) across cohorts. Higher maternal age, education, household income, and physical activity during pregnancy were associated with a better dietary quality and a more anti-inflammatory diet. Conversely, multiparity and smoking during pregnancy were associated with a poorer dietary quality and a more proinflammatory diet. Women with obesity had a poorer pregnancy dietary quality than women with a normal body mass index range., Conclusions: The results will help identify population subgroups who may benefit from targeted public health strategies and interventions aimed at improving women's dietary quality during pregnancy., Competing Interests: Conflicts of interest Dr. James R. Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company that has licensed the right to his invention of the dietary inflammatory index (DII) from the University of South Carolina in order to develop computer and smartphone applications for patient counselling and dietary intervention in clinical settings. Dr. Nitin Shivappa is an employee of CHI. All other authors declare no support from any organisation for the submitted work other than those described above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Exposure to air pollution influences children's health, however, the biological mechanisms underlying these effects are not completely elucidated. We investigated the association between short- and medium-term outdoor air pollution exposure with protein profiles and their link with blood pressure in 1170 HELIX children aged 6-11 years. Different air pollutants (NO 2 , PM 10 , PM 2.5 , and PM 2.5abs ) were estimated based on residential and school addresses at three different windows of exposure (1-day, 1-week, and 1-year before clinical and molecular assessment). Thirty-six proteins, including adipokines, cytokines, or apolipoproteins, were measured in children's plasma using Luminex. Systolic and diastolic blood pressure (SBP and DBP) were measured following a standardized protocol. We performed an association study for each air pollutant at each location and time window and each outcome, adjusting for potential confounders. After correcting for multiple-testing, hepatocyte growth factor (HGF) and interleukin 8 (IL8) levels were positively associated with 1-week home exposure to some of the pollutants (NO 2 , PM 10 , or PM 2.5 ). NO 2 1-week home exposure was also related to higher SBP. The mediation study suggested that HGF could explain 19% of the short-term effect of NO 2 on blood pressure, but other study designs are needed to prove the causal directionality between HGF and blood pressure., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Validated physical activity (PA) questionnaires are crucial for collecting information in large epidemiological studies during childhood. Thus, this study analyzed the validity of a parent-reported PA questionnaire based on the Children’s Leisure Activities Study Survey by accelerometry in European children aged from 6 to 12 years old. We used data from 230 children of the Human Early-Life Exposome and Infancia y Medio Ambiente projects. Mean differences between moderate-to-vigorous PA (MVPA) reported by the questionnaire and the accelerometer were calculated (min/day), and its associated factors were explored by multiple robust linear regression. The agreement between methods was examined using a Bland−Altman plot. The concurrent validity of assessing MVPA was analyzed by cohort-adjusted Spearman’s partial correlations. ROC curve analysis was also used to explore the questionnaire’s capability to identify active children based on the World Health Organization guidelines. A moderate correlation was found between parent-reported and accelerometer MVPA (rho = 0.41, p < 0.001). The child’s sex (girl) was statistically associated with the mean MVPA difference between methods. However, this questionnaire accurately identified physically active children (area under the curve = 83.8% and 82.7% for boys and girls, cut-points = 68.6 and 45.4 min/day in MVPA, respectively). Consequently, this questionnaire is suitable for classifying active children in order to monitor public health interventions regarding PA.

Background: Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children., Methods: We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4-13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration., Results: We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10 -8 ). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10 -8 , n = 577) and sleep onset latency (p = 8.8 × 10 -9 , n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716-2539)., Conclusion: DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available., (© 2022. The Author(s).)

Few studies have examined the associations between parents' own eating behaviors and their feeding practices. We aimed to study the associations between maternal eating behaviors and feeding practices in toddlerhood. In this cross-sectional analysis, maternal eating behaviors and feeding practices were assessed at 2-year follow-up by using the Three-Factor Eating Questionnaire (TFEQ-R21) and the Comprehensive Feeding Practices Questionnaire (CFPQ), respectively, among mothers of 1322 children from the EDEN mother-child cohort. Depending on their distributions, scores from the two questionnaires were considered continuous or binary variables, according to the median. Linear or logistic regression models were used as appropriate to assess the associations between maternal eating behaviors, considered simultaneously in a combined model, and their feeding practices. Maternal cognitive restraint was positively associated with maternal restriction for health and restriction for weight. Maternal uncontrolled eating was positively associated with pressure to eat and use of food to regulate the child's emotions. Maternal uncontrolled eating was also negatively associated with restriction for weight, but only among boys. This study supports that mothers' own eating behaviors are associated with their feeding practices in toddlerhood. Further studies are needed to understand the role of parental feeding practices in the familial transmission of eating behavior., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Importance: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population., Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study., Design, Setting, and Participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022., Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction)., Main Outcomes and Measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups., Results: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units)., Conclusions and Relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

Background: Urban environmental design is increasingly considered influential for health and wellbeing, but evidence is mostly based on adults and single exposure studies. We evaluated the association between a wide range of urban environment characteristics and health behaviours in childhood., Methods: We estimated exposure to 32 urban environment characteristics (related to the built environment, traffic, and natural spaces) for home and school addresses of 1,581 children aged 6-11 years from six European cohorts. We collected information on health behaviours including total amount of overall moderate-to-vigorous physical activity, physical activity outside school hours, active transport, sedentary behaviours and sleep duration, and developed patterns of behaviours with principal component analysis. We used an exposure-wide association study to screen all exposure-outcome associations, and the deletion-substitution-addition algorithm to build a final multi-exposure model., Results: In multi-exposure models, green spaces (Normalized Difference Vegetation Index, NDVI) were positively associated with active transport, and inversely associated with sedentary time (22.71 min/day less (95 %CI -39.90, -5.51) per interquartile range increase in NDVI). Residence in densely built areas was associated with more physical activity and less sedentary time, and densely populated areas with less physical activity outside school hours and more sedentary time. Presence of a major road was associated with lower sleep duration (-4.80 min/day (95 %CI -9.11, -0.48); compared with no major road). Results for the behavioural patterns were similar., Conclusions: This multicohort study suggests that areas with more vegetation, more building density, less population density and without major roads are associated with improved health behaviours in childhood., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Prenatal exposures to endocrine-disrupting chemicals (EDCs) may increase the risk for liver injury in children; however, human evidence is scarce, and previous studies have not considered potential EDC-mixture effects. Furthermore, the association between prenatal EDC exposure and hepatocellular apoptosis in children has not been studied previously., Objective: To investigate associations of prenatal exposure to EDC mixtures with liver injury risk and hepatocellular apoptosis in childhood., Design, Setting, and Participants: This prospective cohort study used data collected from April 1, 2003, to February 26, 2016, from mother-child pairs from the Human Early-Life Exposome project, a collaborative network of 6 ongoing, population-based prospective birth cohort studies from 6 European countries (France, Greece, Lithuania, Norway, Spain, and the UK). Data were analyzed from April 1, 2021, to January 31, 2022., Exposures: Three organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 3 phenols, 4 parabens, 10 phthalates, 4 organophosphate pesticides, 5 perfluoroalkyl substances, and 9 metals., Main Outcomes and Measures: Child serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and CK-18 were measured at 6 to 11 years of age. Risk for liver injury was defined as having ALT, AST, and/or GGT levels above the 90th percentile. Associations of liver injury or cytokeratin 18 (CK-18) levels with each chemical group among the 45 EDCs measured in maternal blood or urine samples collected in pregnancy were estimated using 2 complimentary exposure-mixture methods: bayesian weighted quantile sum (BWQS) and bayesian kernel machine regression., Results: The study included 1108 mothers (mean [SD] age at birth, 31.0 [4.7] years) and their singleton children (mean [SD] age at liver assessment, 8.2 [1.6] years; 598 [54.0%] boys). Results of the BWQS method indicated increased odds of liver injury per exposure-mixture quartile increase for organochlorine pesticides (odds ratio [OR], 1.44 [95% credible interval (CrI), 1.21-1.71]), PBDEs (OR, 1.57 [95% CrI, 1.34-1.84]), perfluoroalkyl substances (OR, 1.73 [95% CrI, 1.45-2.09]), and metals (OR, 2.21 [95% CrI, 1.65-3.02]). Decreased odds of liver injury were associated with high-molecular-weight phthalates (OR, 0.74 [95% CrI, 0.60-0.91]) and phenols (OR, 0.66 [95% CrI, 0.54-0.78]). Higher CK-18 levels were associated with a 1-quartile increase in polychlorinated biphenyls (β, 5.84 [95% CrI, 1.69-10.08] IU/L) and PBDEs (β, 6.46 [95% CrI, 3.09-9.92] IU/L). Bayesian kernel machine regression showed associations in a similar direction as BWQS for all EDCs and a nonlinear association between phenols and CK-18 levels., Conclusions and Relevance: With a combination of 2 state-of-the-art exposure-mixture approaches, consistent evidence suggests that prenatal exposures to EDCs are associated with higher risk for liver injury and CK-18 levels and constitute a potential risk factor for pediatric nonalcoholic fatty liver disease.

The preconception period represents an important window for foetal and epigenetic programming. Some micronutrients (B vitamins, choline, betaine, methionine) implicated in one-carbon metabolism (OCM) are essential for major epigenetic processes that take place in early pregnancy. However, few studies have evaluated the implication of the micronutrients in placental DNA methylation. We investigated whether intake of OCM nutrients in the year before pregnancy was associated with placental DNA methylation in the EDEN mother-child cohort. Maternal dietary intake was assessed with a food-frequency questionnaire. Three dietary patterns, 'varied and balanced diet,' 'vegetarian tendency,' and 'bread and starchy food,' were used to characterize maternal OCM dietary intake. The Illumina Infinium HumanMethylation450 BeadChip was used to measure placental DNA methylation of 573 women included in the analyses. We evaluated the association of dietary patterns with global DNA methylation. Then, we conducted an agnostic epigenome-wide association study (EWAS) and investigated differentially methylated regions (DMRs) associated with each dietary pattern. We found no significant association between the three dietary patterns and global DNA methylation or individual CpG sites. DMR analyses highlighted associations between the 'varied and balanced' or 'vegetarian tendency' pattern and DMRs located at genes previously implicated in functions essential for embryonic development, such as neurodevelopment. The 'bread and starchy food' pattern was associated with regions related to genes whose functions involve various metabolic and cell synthesis-related processes. In mainly well-nourished French women without major deficiencies, OCM intake before pregnancy was not associated with major variation in DNA methylation.

Background: Maternal smoking during pregnancy has adverse health effects on the offspring, including lower birth weight and increased risk for obesity. These outcomes are also influenced by common genetic polymorphisms. We aimed to investigate the combined effect of maternal smoking during pregnancy and genetic predisposition on birth weight and body mass index (BMI)-related traits in 1,086 children of the Human Early Life Exposome (HELIX) project. Methods: Maternal smoking during pregnancy was self-reported. Phenotypic traits were assessed at birth or at the age of 8 years. Ten polygenic risk scores (PRSs) per trait were calculated using the PRSice v2 program. For birth weight, we estimated two sets of PRSs based on two different base GWAS summary statistics: PRS-EGG, which includes HELIX children, and PRS-PanUK, which is completely independent. The best PRS per trait (highest R 2 ) was selected for downstream analyses, and it was treated in continuous or categorized into three groups. Multivariate linear regression models were applied to evaluate the association of the explanatory variables with the traits of interest. The combined effect was evaluated by including an interaction term in the regression models and then running models stratified by the PRS group. Results: BMI-related traits were correlated among them but not with birth weight. A similar pattern was observed for their PRSs. On average, the PRSs explained ∼4% of the phenotypic variation, with higher PRS values related to higher trait values ( p -value <5.55E-08). Sustained maternal smoking was associated with lower birth weight and higher BMI and related traits ( p -value <2.99E-02). We identified a gene by environment (GxE) interaction for birth weight between sustained maternal smoking and the PRS-EGG in three groups ( p -value interaction = 0.01), which was not replicated with the PRS-PanUK ( p -value interaction = 0.341). Finally, we did not find any statistically significant GxE interaction for BMI-related traits ( p -value interaction >0.237). Conclusion: Sustained maternal smoking and the PRSs were independently associated with birth weight and childhood BMI-related traits. There was low evidence of GxE interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fuentes-Paez, Escaramís, Aguilar-Lacasaña, Andrusaityte, Brantsæter, Casas, Charles, Chatzi, Lepeule, Grazuleviciene, Gützkow, Heude, Maitre, Ruiz-Arenas, Sunyer, Urquiza, Yang, Wright, Vrijheid, Vilor-Tejedor and Bustamante.)

Maternal diet is the main source of fatty acids for developing offspring in-utero and in breastfed infants. Dairy products (DP) are important sources of fat in the European population diet. C15:0 and C17:0 fatty acids have been suggested as biomarkers of dairy fat consumption. This study's aim is to describe the associations between maternal DP (milk included) consumption during pregnancy and C15:0, C17:0 and polyunsaturated fatty acid (PUFA) levels in perinatal biofluids. Study populations were composed of 1763, 1337 and 879 French mothers from the EDEN ("Étude des Déterminants pre- et post-natals de la santé de l'ENfant") study, with data on maternal and cord red blood cells' (RBC) membrane and colostrum, respectively. Associations were assessed using linear regression models adjusted for recruitment center, maternal age, healthy dietary pattern or fish consumption. Greater adherence to a "cheese" consumption pattern was associated with lower linoleic acid level in colostrum and higher C15:0 and C17:0 levels but in a less consistent manner for C17:0 across biofluids. Greater adherence to "semi-skimmed milk, yogurt" and "reduced-fat DP" patterns was related to higher docosahexaenoic acid and total n-3 PUFA levels and lower n-6/n-3 long-chain PUFA ratio in maternal and cord RBC. Our results suggest that C15:0 could be a good biomarker of maternal dairy fat consumption in perinatal biofluids.

Background: Early childhood may represent an opportune time to commence primordial prevention of cardiovascular disease (CVD, i.e., prevention of risk factors onset), but epidemiological evidence is scarce. We aimed to examine the distribution and parental and early life determinants of ideal cardiovascular health (CVH) in children up to 5 years and to compare the level of cognitive development between children with and without ideal CVH at age 5 years., Methods: Using data from the Etude sur les déterminants pré et post natals précoces du Développement psychomoteur et de la santé de l'Enfant (EDEN) study, a French population-based mother-child cohort study, CVH was examined in children at 5 years of age based on the American Heart Association CVH metrics (ideal body mass index, physical activity, diet, blood pressure, cholesterol and glucose levels, and passive smoking, considered in sensitivity analysis only). Children were categorized as having ideal (five to six ideal metrics) or non-ideal CVH (<5 ideal metrics). Intelligence quotient (IQ) at age 5 years was assessed using the French version of the Wechsler Preschool and Primary Scale of Intelligence., Results: Among the 566 children (55% boys), only 34% had ideal CVH. In fully adjusted logistic regression, boys compared to girls (OR = 1.77, 95% CI 1.13-2.78), children with intermediate (1.77, 1.05-2.98) or ideal (2.58, 1.38-4.82) behavioral CVH at age 3 years and children who spent < 30 min/day watching television (1.91, 1.09-3.34) at age 3 years were more likely to have ideal CVH at age 5 years. At age 5 years, there was a significant 2.98-point difference (95% CI 0.64-5.32) in IQ between children with and without ideal biological CVH after adjusting for confounders., Conclusion: This study highlights that only a third of children aged 5 years had ideal CVH and identified modifiable determinants of ideal CVH and is suggestive of an association between CVH and neurodevelopment at a young age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Climie, Tafflet, Sloten, Lauzon-Guillain, Bernard, Dargent-Molina, Plancoulaine, Lioret, Jouven, Charles, Heude and Empana.)

Background/objective: High magnitude of adiposity peak and early adiposity rebound are early risk markers of later obesity. Infant diet represents one of the main modifiable determinants of early growth. This study aimed to investigate the association between infant feeding practices and age and magnitude of adiposity peak and rebound., Subjects/methods: Analyses were based on data from the French EDEN mother-child cohort. Data on breastfeeding and complementary feeding were collected at birth and 4, 8, and 12 months. From clinical examinations and measurements collected in the child's health booklet up to 12 years, individual growth curves were modeled, and ages and magnitudes of adiposity peak and rebound were estimated. Associations between infant feeding practices and growth were investigated by multivariable linear regression in children after testing a child-sex interaction., Results: In the studied population (n = 1225), adiposity peak occurred at a mean of 9.9 ± 2 months and adiposity rebound at 5.5 ± 1.4 years. Associations between infant feeding practices and adiposity peak or rebound were moderated by child sex. For girls, each additional month of breastfeeding was related to a 2-day increase in the age at adiposity peak (p < 0.001), and an 18-day increase in the age at adiposity peak (p = 0.004). Whereas for boys, each additional month for the age at complementary food introduction was associated with a 29-day increase in the age at adiposity rebound (p = 0.02). For boys, long breastfeeding duration was only related to reduced body mass index at adiposity peak., Conclusions: Child sex has a moderating effect on the association between infant feeding practices and adiposity peak or rebound. The well-known association between breastfeeding duration and early growth seems stronger in girls than boys. The association found for complementary feeding in boys may give new insights into preventing obesity., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Customized intrauterine growth charts are widely used for growth monitoring and research. They are based on three assumptions: (1) estimated fetal weight (EFW) has a normal distribution with a constant coefficient of variation at all gestational ages; (2) Hadlock's growth curve accurately describes the relation between EFW and gestational ages; (3) associations between EFW and the fetal and maternal characteristics included in the customization model (fetal sex, pre-pregnancy weight, height, parity) are proportional throughout pregnancy. The aim of this study was to test whether these underlying assumptions are verified., Material and Methods: Data came from (1) the French Longitudinal Study of Children (ELFE) cohort, which recruited births after 32 weeks' gestation in 349 maternity hospitals in France in 2011, and (2) the National Perinatal Survey, which included births from all French maternity hospitals in 2016. The study population included, respectively, 6 920 and 8 969 singleton non-malformed term live births with data on customization characteristics and EFW. We computed the coefficient of variation by gestational age and then modeled the association of gestational age, maternal and fetal characteristics with EFW at the second and third trimester ultrasound and with birthweight using linear regression. To assess the proportionality of the impact of maternal and fetal characteristics, we computed the percent change in weight associated with these characteristics at these three time points., Results: The coefficient of variation was close to 12% at each gestational age, but EFW was not normally distributed, leading to small but systematic underestimation of fetuses under the 10th percentile. Weights representing the 50th and 10th percentiles based on Hadlock's growth trajectory were lower than observed or predicted weights. Most characteristics more strongly impacted weight at birth than during pregnancy. In the French Longitudinal study of Children (ELFE) cohort, boys were 1.8% (95% confidence interval [CI] 1.3-2.4) heavier than girls in the third trimester, whereas this percentage was 4.6% (95% CI 4.0-5.2) at birth. In the National Perinatal Survey, these percentages were 2.3% (95% CI 1.8-2.8) and 4.3% (95% CI 3.8-4.8)., Conclusions: These results from two independent sources revealed discrepancies between routine clinical EFW data used for growth monitoring and the customized growth model's assumptions., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses., Purpose: Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors., Methods: Ten behavioural variables related to child's diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5-6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression., Results: Three broadly similar lifestyle patterns were identified in both cohorts: "discretionary consumption and high screen time", "fruit, vegetables, and low screen time" and "high outdoor playtime and walking". The latter two patterns showed small differences between cohorts and sexes. The "discretionary consumption and high screen time" pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating., Conclusions: Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health., (© 2022. The Author(s).)

Association of phenotypes or exposures with genomic and epigenomic data faces important statistical challenges. One of these challenges is to account for variation due to unobserved confounding factors, such as individual ancestry or cell-type composition in tissues. This issue can be addressed with penalized latent factor regression models, where penalties are introduced to cope with high dimension in the data. If a relatively small proportion of genomic or epigenomic markers correlate with the variable of interest, sparsity penalties may help to capture the relevant associations, but the improvement over non-sparse approaches has not been fully evaluated yet. Here, we present least-squares algorithms that jointly estimate effect sizes and confounding factors in sparse latent factor regression models. In simulated data, sparse latent factor regression models generally achieved higher statistical performance than other sparse methods, including the least absolute shrinkage and selection operator and a Bayesian sparse linear mixed model. In generative model simulations, statistical performance was slightly lower (while being comparable) to non-sparse methods, but in simulations based on empirical data, sparse latent factor regression models were more robust to departure from the model than the non-sparse approaches. We applied sparse latent factor regression models to a genome-wide association study of a flowering trait for the plant Arabidopsis thaliana and to an epigenome-wide association study of smoking status in pregnant women. For both applications, sparse latent factor regression models facilitated the estimation of non-null effect sizes while overcoming multiple testing issues. The results were not only consistent with previous discoveries, but they also pinpointed new genes with functional annotations relevant to each application., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: To evaluate the applicability of World Health Organization (WHO) fetal growth charts for abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) at the second and third trimester ultrasounds in a French birth cohort., Materials and Methods: Using the ELFE cohort of live births after 33 weeks' gestation in France in 2011, we selected 7747 singletons with fetal biometric measurements at the second (20-25 weeks) and third (30-35 weeks) trimester routine ultrasounds. We calculated proportions of fetuses <3rd and <10th percentiles and >90th and >97th percentiles for AC, FL and EFW using WHO charts and two international (Intergrowth and Hadlock) and two national (Salomon and CFEF) charts. Analyses were also carried out in a subsample of 4427 low-risk births., Results: WHO charts classified 2,3% and 8-10% of fetuses <3rd and <10th percentiles respectively, for AC and FL in the second and third trimesters and EFW in the third trimester. Similarly, about 3 and 10% of fetuses had AC, FL and EFW >97th and >90th percentile in both trimesters. Hadlock and CFEF charts also provided a good fit for third-trimester EFW <10th percentile. For most measures, Intergrowth yielded low proportions <3rd and <10th percentile, and high proportions >90th and >97th percentiles. Proportions were slightly lower for low-risk pregnancies., Conclusion: WHO charts provided a good description of the distribution of French fetal biometric measures. Further research is needed to assess the impact of using WHO charts on obstetrical management and perinatal outcomes., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)